The objectives of these studies are: (1)\to determine the concentration of Ca2+ present within normal and malignant tissues; (2)\to elucidate the role that each Ca2+ transport process plays in regulating the level and distribution of intracellular Ca2+; (3)\to establish whether physio-logically significant alterations exist in the regulation of intracellular Ca2+ or the control of cellular activities by Ca2+ in tumor cells. These objectives and the specific aims of the research are supported by the observations that alterations of Ca2+ metabolism can explain many abnormal characteristics of malignant cells--tumor cells grown in vitro proliferate at a much lower extracellular Ca2+ concentration than that required by normal cells; abnormalities of intracellular Ca2+ metabolism apparently do exist in some types of tumors. The specific aims of this research are: (1)\to determine the cytosolic free Ca2+ concentration and the intracellulardistribution of Ca2+ in hepatocytes (isolated from normal and regenerating liver) as well as malignant hepatoma cells and Ehrlich ascites tumor cells; (2)\to determine the Ca2+ buffering characteristics of mitochondria and endoplasmic reticulum under physiologically realistic conditions; (3)\to better understand the inhibition of oxidative phosphorylation by Ca2+ in normal and neoplastic cells; (4)\to compare the effects of Ca2+ on the cytoskeleton of normal and malignant tissues.